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1.
Eur Rev Med Pharmacol Sci ; 28(5): 1797-1811, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38497863

RESUMO

OBJECTIVE: Perioperative anxiety and depression syndrome (PADS) is a common clinical concern among women with systemic tumors. Esketamine has been considered for its potential to alleviate anxiety and depressive symptoms. However, its specific application and effectiveness in PADS among women with systemic tumors remain unclear. This study aimed to analyze the utility of Machine Learning (ML) algorithms based on electroencephalogram (EEG) signals in evaluating perioperative anxiety and depression in women with systemic tumors treated with Esketamine, utilizing a large-scale medical data background. PATIENTS AND METHODS: A single-center, randomized, placebo-controlled (SC-RPC) trial design was adopted. A total of 112 female patients with systemic tumors and PADS who received Esketamine treatment were included as study participants. A moderate dose (0.7 mg/kg) of Esketamine was administered through intravenous infusion over a duration of 60 minutes. EEG signals were collected from all patients, and the EEG signal features of individuals with depression were compared to those without depression. In this study, a Support Vector Machine (SVM)-K-Nearest Neighbour (KNN) hybrid classifier was constructed based on SVM and KNN algorithms. Using the EEG signals, the classifier was utilized to assess the anxiety and depression status of the patients. The predictive performance of the classifier was evaluated using accuracy, sensitivity, and specificity measures. RESULTS: The C2 correntropy feature of the delta rhythm in the left-brain EEG signal was significantly higher in individuals with depression compared to those without depression (p<0.05). Moreover, the C2 correntropy feature of the Alpha, Beta, and Gamma rhythms in the left-brain EEG signal was significantly lower in individuals with depression compared to those without depression (p<0.05). In the right brain EEG signal, the C2 correntropy feature of the delta rhythm was significantly higher in individuals with depression (p<0.05), while the C2 correntropy feature of the alpha and gamma rhythms was significantly lower in individuals with depression compared to those without depression (p<0.05). Additionally, the C1 correntropy feature of the Gamma rhythm in the right brain EEG signal was significantly higher in individuals with depression compared to those without depression (p<0.05). The SVM classifier achieved accuracy, sensitivity, and specificity of 98.23%, 98.10%, and 98.56%, respectively, in recognizing the left-brain EEG signals, with a correlation coefficient of 0.95. In recognizing the right brain EEG signals, the SVM classifier achieved accuracy, sensitivity, and specificity of 98.74%, 98.43%, and 99.03%, respectively, with a correlation coefficient of 0.96. The improved SVM-KNN approach yielded an accuracy, recall, precision, F-score, area over the curve (AOC), and Receiver Operation Characteristics (ROC) of 0.829, 0.811, 0.791, 0.853, 0.787, and 0.877, respectively, in predicting anxiety. For predicting depression, the accuracy, recall, precision, F-score, AOC, and ROC were 0.869, 0.842, 0.831, 0.893, 0.827, and 0.917, respectively. CONCLUSIONS: Significant differences were observed in the brain EEG signals between individuals with depression and those without depression. The improved SVM-KNN algorithm developed in this study demonstrates good predictive capability for anxiety and depression.


Assuntos
Big Data , Ketamina , Neoplasias , Feminino , Humanos , Depressão/diagnóstico , Depressão/tratamento farmacológico , Ritmo Gama , Ansiedade/diagnóstico , Ansiedade/tratamento farmacológico , Síndrome
2.
Nature ; 627(8002): 149-156, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38418876

RESUMO

The glymphatic movement of fluid through the brain removes metabolic waste1-4. Noninvasive 40 Hz stimulation promotes 40 Hz neural activity in multiple brain regions and attenuates pathology in mouse models of Alzheimer's disease5-8. Here we show that multisensory gamma stimulation promotes the influx of cerebrospinal fluid and the efflux of interstitial fluid in the cortex of the 5XFAD mouse model of Alzheimer's disease. Influx of cerebrospinal fluid was associated with increased aquaporin-4 polarization along astrocytic endfeet and dilated meningeal lymphatic vessels. Inhibiting glymphatic clearance abolished the removal of amyloid by multisensory 40 Hz stimulation. Using chemogenetic manipulation and a genetically encoded sensor for neuropeptide signalling, we found that vasoactive intestinal peptide interneurons facilitate glymphatic clearance by regulating arterial pulsatility. Our findings establish novel mechanisms that recruit the glymphatic system to remove brain amyloid.


Assuntos
Doença de Alzheimer , Amiloide , Encéfalo , Líquido Cefalorraquidiano , Líquido Extracelular , Ritmo Gama , Sistema Glinfático , Animais , Camundongos , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Doença de Alzheimer/prevenção & controle , Amiloide/metabolismo , Aquaporina 4/metabolismo , Astrócitos/metabolismo , Encéfalo/citologia , Encéfalo/metabolismo , Encéfalo/patologia , Líquido Cefalorraquidiano/metabolismo , Modelos Animais de Doenças , Líquido Extracelular/metabolismo , Sistema Glinfático/fisiologia , Interneurônios/metabolismo , Peptídeo Intestinal Vasoativo/metabolismo , Córtex Cerebral/citologia , Córtex Cerebral/metabolismo , Córtex Cerebral/patologia , Estimulação Elétrica
3.
J Trace Elem Med Biol ; 72: 126993, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35550983

RESUMO

BACKGROUND: Lead (Pb) is one of the most hazardous pollutants that induce a wide spectrum of neurological changes such as learning and memory deficits. Sesamin, a phytonutrient of the lignan class, exhibits anti-inflammatory, anti-apoptotic, and neuroprotective properties. The present study was designed to investigate the effects of sesamin against Pb-induced learning and memory deficits, disruption of hippocampal theta and gamma rhythms, inflammatory response, inhibition of blood δ-aminolevulinic acid dehydratase (δ-ALA-D) activity, Pb accumulation, and neuronal loss in rats. METHODS: Sesamin treatment (30 mg/kg/day; P.O.) was started simultaneously with Pb acetate exposure (500 ppm in standard drinking water) in rats, and they continued for eight consecutive weeks. RESULTS: The results showed that chronic exposure to Pb disrupted the learning and memory functions in both passive-avoidance and water-maze tests, which was accompanied by increase in spectral theta power and theta/gamma ratio, and a decrease in spectral gamma power in the hippocampus. Additionally, Pb exposure resulted in an enhanced tumor necrosis factor-alpha (TNF-α) content, decreased interleukin-10 (IL-10) production, inhibited blood δ-ALA-D activity, increased Pb accumulation, and neuronal loss of rats. In contrast, sesamin treatment improved all the above-mentioned Pb-induced pathological changes. CONCLUSION: This data suggests that sesamin could improve Pb-induced learning and memory deficits, possibly through amelioration of hippocampal theta and gamma rhythms, modulation of inflammatory status, restoration of the blood δ-ALA-D activity, reduction of Pb accumulation in the blood and the brain tissues, and prevention of neuronal loss.


Assuntos
Chumbo , Lignanas , Animais , Dioxóis , Ritmo Gama , Hipocampo , Chumbo/toxicidade , Lignanas/farmacologia , Lignanas/uso terapêutico , Aprendizagem em Labirinto , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/tratamento farmacológico , Transtornos da Memória/patologia , Ratos
4.
Cell Rep ; 38(7): 110383, 2022 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-35172159

RESUMO

In the olfactory bulb (OB), olfactory information represented by mitral/tufted cells (M/Ts) is extensively modulated by local inhibitory interneurons before being transmitted to the olfactory cortex. While the crucial roles of cortical vasoactive-intestinal-peptide-expressing (VIP) interneurons have been extensively studied, their precise function in the OB remains elusive. Here, we identify the synaptic connectivity of VIP interneurons onto mitral cells (MCs) and demonstrate their important role in olfactory behaviors. Optogenetic activation of VIP interneurons reduced both spontaneous and odor-evoked activity of M/Ts in awake mice. Whole-cell recordings revealed that VIP interneurons decrease MC firing through direct inhibitory synaptic connections with MCs. Furthermore, inactivation of VIP interneurons leads to increased MC firing and impaired olfactory detection and odor discrimination. Therefore, our results demonstrate that VIP interneurons control OB output and play critical roles in odor processing and olfactory behaviors.


Assuntos
Discriminação Psicológica , Interneurônios/fisiologia , Odorantes , Bulbo Olfatório/fisiologia , Peptídeo Intestinal Vasoativo/metabolismo , Animais , Ritmo beta/fisiologia , Feminino , Ritmo Gama/fisiologia , Masculino , Camundongos , Inibição Neural/fisiologia , Sinapses/fisiologia , Vigília/fisiologia
5.
Neurobiol Dis ; 159: 105514, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34555537

RESUMO

Synchronized and properly balanced electrical activity of neurons is the basis for the brain's ability to process information, to learn, and to remember. In Alzheimer's disease (AD), which causes cognitive decline in patients, this synchronization and balance is disturbed by the accumulation of neuropathological biomarkers such as amyloid-beta peptide (Aß42). Failure of Aß42 clearance mechanisms as well as desynchronization of crucial neuronal classes such as fast-spiking interneurons (FSN) are root causes for the disruption of the cognition-relevant gamma brain rhythm (30-80 Hz) and consequent cognitive impairment observed in AD. Here we show that recombinant BRICHOS molecular chaperone domains from ProSP-C or Bri2, which interfere with Aß42 aggregation, can rescue the gamma rhythm. We demonstrate that Aß42 progressively decreases gamma oscillation power and rhythmicity, disrupts the inhibition/excitation balance in pyramidal cells, and desynchronizes FSN firing during gamma oscillations in the hippocampal CA3 network of mice. Application of the more efficacious Bri2 BRICHOS chaperone rescued the cellular and neuronal network performance from all ongoing Aß42-induced functional impairments. Collectively, our findings offer critical missing data to explain the importance of FSN for normal network function and underscore the therapeutic potential of Bri2 BRICHOS to rescue the disruption of cognition-relevant brain rhythms in AD.


Assuntos
Potenciais de Ação/efeitos dos fármacos , Proteínas Adaptadoras de Transdução de Sinal/farmacologia , Hipocampo/efeitos dos fármacos , Interneurônios/efeitos dos fármacos , Chaperonas Moleculares/farmacologia , Células Piramidais/efeitos dos fármacos , Potenciais de Ação/fisiologia , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Peptídeos beta-Amiloides , Animais , Modelos Animais de Doenças , Ritmo Gama , Hipocampo/fisiopatologia , Técnicas In Vitro , Interneurônios/fisiologia , Camundongos , Vias Neurais/efeitos dos fármacos , Vias Neurais/fisiopatologia , Fragmentos de Peptídeos , Domínios Proteicos , Proteína C Associada a Surfactante Pulmonar/metabolismo , Proteína C Associada a Surfactante Pulmonar/farmacologia , Células Piramidais/metabolismo , Células Piramidais/fisiologia , Proteínas Recombinantes
6.
Clin Neurophysiol ; 132(10): 2391-2403, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34454266

RESUMO

OBJECTIVE: We clarified the clinical and mechanistic significance of physiological modulations of high-frequency broadband cortical activity associated with spontaneous saccadic eye movements during a resting state. METHODS: We studied 30 patients who underwent epilepsy surgery following extraoperative electrocorticography and electrooculography recordings. We determined whether high-gamma activity at 70-110 Hz preceding saccade onset would predict upcoming ocular behaviors. We assessed how accurately the model incorporating saccade-related high-gamma modulations would localize the primary visual cortex defined by electrical stimulation. RESULTS: The dynamic atlas demonstrated transient high-gamma suppression in the striatal cortex before saccade onset and high-gamma augmentation subsequently involving the widespread posterior brain regions. More intense striatal high-gamma suppression predicted the upcoming saccade directed to the ipsilateral side and lasting longer in duration. The bagged-tree-ensemble model demonstrated that intense saccade-related high-gamma modulations localized the visual cortex with an accuracy of 95%. CONCLUSIONS: We successfully animated the neural dynamics supporting saccadic suppression, a principal mechanism minimizing the perception of blurred vision during rapid eye movements. The primary visual cortex per se may prepare actively in advance for massive image motion expected during upcoming prolonged saccades. SIGNIFICANCE: Measuring saccade-related electrocorticographic signals may help localize the visual cortex and avoid misperceiving physiological high-frequency activity as epileptogenic.


Assuntos
Epilepsia Resistente a Medicamentos/fisiopatologia , Eletrocorticografia/métodos , Ritmo Gama/fisiologia , Movimentos Sacádicos/fisiologia , Córtex Visual/fisiologia , Adolescente , Criança , Pré-Escolar , Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Feminino , Humanos , Masculino , Córtex Visual/diagnóstico por imagem , Adulto Jovem
7.
Rev. bras. med. esporte ; 27(4): 405-409, Aug. 2021. graf
Artigo em Inglês | LILACS | ID: biblio-1288596

RESUMO

ABSTRACT Objective: The paper uses artificial neural network images to explore the effects of aerobic exercise on the gamma rhythm of theta period in the awake hippocampal CA1 area of APP/PS1/tau mice and the low-frequency gamma rhythm of the sleep state hippocampal CA1 area SWR period. Methods: Clean grade 6-month-old APP/PS1/tau mice were randomly divided into quiet group (AS) and exercise group (AE), C57BL/6J control group mice were randomly divided into quiet group (CS) and exercise group (CE). The AE group and the CE group performed 12-week treadmill exercise, 5d/week, 60min/d, the first 10min exercise load was 12m/min, the last 50min was 15m/min treadmill slope was 0°. Eight-arm maze detection of behavioral changes in mice; multi-channel in vivo recording technology to record the electrical signals of the awake state and sleep state in the hippocampal CA1 area, MATLAB extracts the awake state theta period and sleep state SWR period, multi-window spectrum estimation method Perform time-frequency analysis and power spectral density analysis. Results: 12 weeks of aerobic exercise can significantly improve the working memory and reference memory of the AS group, increase the gamma energy in theta period of the awake hippocampus CA1 area and the low-frequency gamma energy in the sleep state CA1 area SWR period. Conclusions: Aerobic exercise can improve the neural network state of the AD model and increase the gamma energy in theta period of the hippocampus CA1 area, and the low-frequency gamma energy in the SWR period is one of the neural network mechanisms for its overall behavioral improvement. Level of evidence II; Therapeutic studies - investigation of treatment results.


RESUMO Objetivo: o artigo usa imagens de redes neurais artificiais para explorar os efeitos do exercício aeróbio no ritmo gama do período teta na área CA1 do hipocampo desperto de camundongos APP/PS1/tau e o ritmo gama de baixa frequência da área CA1 do hipocampo do estado de sono Período SWR. Métodos: Camundongos APP/PS1/tau de grau limpo de 6 meses de idade foram divididos aleatoriamente em grupo quieto (AS) e grupo de exercício (AE), os camundongos do grupo controle C57BL/6J foram divididos aleatoriamente em grupo quieto (CS) e grupo de exercício (CE). O grupo AE e o grupo CE realizaram 12 semanas de exercício em esteira, 5d/semana, 60min/d, a primeira carga de exercício de 10min foi de 12m/min, a última de 50min foi de 15m/min e a inclinação da esteira foi de 0 °. Detecção de labirinto de oito braços de mudanças comportamentais em camundongos; tecnologia de gravação in vivo multicanal para registrar os sinais elétricos do estado de vigília e do estado de sono na área CA1 do hipocampo, MATLAB extrai o período de tempo teta do estado de vigília e o período de tempo SWR do estado de sono, método de estimativa de espectro de múltiplas janelas. e análise de densidade espectral de potência. Resultados: 12 semanas de exercícios aeróbicos podem melhorar significativamente a memória de trabalho e a memória de referência do grupo AS, aumentar a energia gama no período teta da área CA1 do hipocampo acordado e a energia gama de baixa frequência na área CA1 do estado de sono período SWR. Conclusões: O exercício aeróbico pode melhorar o estado da rede neural do modelo AD e aumentar a energia gama no período teta da área CA1 do hipocampo e a energia gama de baixa frequência no período SWR é um dos mecanismos da rede neural para seu comportamento geral. Nível de evidência II; Estudos terapêuticos- investigação dos resultados do tratamento.


RESUMEN Objetivo: El artículo utiliza imágenes de redes neuronales artificiales para explorar los efectos del ejercicio aeróbico en el ritmo gamma del período theta en el área CA1 del hipocampo despierto de ratones APP/PS1/tau y el ritmo gamma de baja frecuencia del área CA1 del hipocampo en estado de sueño. Período de ROE. Métodos: Se dividieron aleatoriamente ratones APP/PS1/tau de 6 meses de edad de grado limpio en grupo tranquilo (AS) y grupo de ejercicio (AE), los ratones del grupo de control C57BL/6J se dividieron aleatoriamente en grupo tranquilo (CS) y grupo de ejercicio (CE). El grupo de EA y el grupo de EC realizaron 12 semanas de ejercicio en cinta rodante, 5 días a la semana, 60 min/d, la primera carga de ejercicio de 10 min fue de 12 m/min, los últimos 50 min fueron de 15 m/min y la pendiente de la cinta fue de 0 °. Detección en laberinto de ocho brazos de cambios de comportamiento en ratones; tecnología de grabación in vivo multicanal para registrar las señales eléctricas del estado despierto y del estado de sueño en el área CA1 del hipocampo, MATLAB extrae el período de tiempo theta del estado despierto y el período de tiempo de SWR del estado de suspensión, método de estimación de espectro de múltiples ventanas Realizar análisis de tiempo-frecuencia y análisis de densidad espectral de potencia. Resultados: 12 semanas de ejercicio aeróbico pueden mejorar significativamente la memoria de trabajo y la memoria de referencia del grupo AS, aumentar la energía gamma en el período theta del área CA1 del hipocampo despierto y la energía gamma de baja frecuencia en el período SWR del área CA1 del estado de sueño. Conclusiones: El ejercicio aeróbico puede mejorar el estado de la red neuronal del modelo AD y aumentar la energía gamma en el período theta del área del hipocampo CA1 y la energía gamma de baja frecuencia en el período SWR es uno de los mecanismos de la red neuronal para su comportamiento general. Nivel de evidencia II; Estudios terapéuticos- investigación de los resultados del tratamiento.


Assuntos
Animais , Camundongos , Exercício Físico/fisiologia , Redes Neurais de Computação , Ritmo Gama/fisiologia , Hipocampo/diagnóstico por imagem , Modelos Animais
8.
Clin Neurophysiol ; 132(8): 1927-1936, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34157635

RESUMO

OBJECTIVE: Epilepsy surgery fails in > 30% of patients with focal cortical dysplasia (FCD). The seizure persistence after surgery can be attributed to the inability to precisely localize the tissue with an endogenous potential to generate seizures. In this study, we aimed to identify the critical components of the epileptic network that were actively involved in seizure genesis. METHODS: The directed transfer function was applied to intracranial EEG recordings and the effective connectivity was determined with a high temporal and frequency resolution. Pre-ictal network properties were compared with ictal epochs to identify regions actively generating ictal activity and discriminate them from the areas of propagation. RESULTS: Analysis of 276 seizures from 30 patients revealed the existence of a seizure-related network reconfiguration in the gamma-band (25-170 Hz; p < 0.005) - ictogenic nodes. Unlike seizure onset zone, resecting the majority of ictogenic nodes correlated with favorable outcomes (p < 0.012). CONCLUSION: The prerequisite to successful epilepsy surgery is the accurate identification of brain areas from which seizures arise. We show that in FCD-related epilepsy, gamma-band network markers can reliably identify and distinguish ictogenic areas in macroelectrode recordings, improve intracranial EEG interpretation and better delineate the epileptogenic zone. SIGNIFICANCE: Ictogenic nodes localize the critical parts of the epileptogenic tissue and increase the diagnostic yield of intracranial evaluation.


Assuntos
Córtex Cerebral/fisiopatologia , Epilepsia Resistente a Medicamentos/fisiopatologia , Ritmo Gama/fisiologia , Malformações do Desenvolvimento Cortical/fisiopatologia , Rede Nervosa/fisiopatologia , Adolescente , Adulto , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/cirurgia , Criança , Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Epilepsia Resistente a Medicamentos/cirurgia , Feminino , Seguimentos , Humanos , Masculino , Malformações do Desenvolvimento Cortical/diagnóstico por imagem , Malformações do Desenvolvimento Cortical/cirurgia , Pessoa de Meia-Idade , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/cirurgia , Estudos Retrospectivos , Adulto Jovem
9.
Phys Eng Sci Med ; 44(1): 157-171, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33417158

RESUMO

Surgery is recommended for epilepsy diagnosis in cases where patients do not respond well to anti-epilepsy medications. Successful surgery is essentially dependent on the area suffered from epilepsy, i.e., focal area. Electroencephalogram (EEG) signals are considered a powerful tool to identify focal or non-focal (normal) areas. In this work, we propose an automated method for focal and non-focal EEG signal identification, taking into account non-linear features derived from rhythms in the empirical wavelet transform (EWT) domain. The research paradigm is related to the decomposition of EEG signals into the delta, theta, alpha, beta, and gamma rhythms through the development of the EWT. Specifically, various non-linear features are extracted from rhythms composed of Stein's unbiased risk estimation entropy, threshold entropy, centered correntropy, and information potential. From a statistical point of view, Kruskal-Wallis (KW) statistical test is then used to identify the significant features. The significant features obtained from the KW test are fed to support vector machine (SVM) and k-nearest neighbor (KNN) classifiers. The SURE entropy provides an average classification accuracy of 93% and 82.6% for small and entire datasets by utilizing SVM and KNN classifiers with a tenfold cross-validation method, respectively. It is observed that the proposed method is better and competitive in comparison with other studies for small and large data, respectively. The obtained outcome concludes that the proposed framework could be used for people with epilepsy and can help the physicians to validate the assessment.


Assuntos
Ritmo Gama , Análise de Ondaletas , Algoritmos , Eletroencefalografia , Humanos , Máquina de Vetores de Suporte
10.
Neuromolecular Med ; 23(3): 416-427, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33398803

RESUMO

Theta and gamma rhythms in hippocampus are important to cognitive performance. The cognitive impairments following cerebral ischemia is linked with the dysfunction of theta and gamma oscillations. As the primary mechanism for learning and memory, synaptic plasticity is in connection with these neural oscillations. Although vascular endothelial growth factor (VEGF) is thought to protect synaptic function in the ischemia rats to relieve cognitive impairment, little has been done on its effect of neural dynamics with this process. The present study investigated whether the alternation of neural oscillations in the hippocampus of ischemia rats is one of the potential neuroprotective mechanisms of VEGF. Rats were treated with the intranasal administration of VEGF at 72 h following chronic global cerebral ischemia procedure. Then local field potentials (LFPs) in hippocampal CA1 and CA3 regions were recorded and analyzed. Our results showed that VEGF can improve the power of theta and gamma rhythms in CA1 region after ischemia. Chronic global cerebral ischemia reduced the theta-gamma phase-amplitude coupling (PAC) not only within CA1 area but also in the pathway from CA3 to CA1, while VEGF alleviated the decreased coupling strength. Despite these notable differences, there were no obvious changes in the PAC within CA3 region. Surprisingly, the ischemia state did not affect the phase-phase interaction of hippocampus. In conclusion, our findings demonstrated that VEGF enhanced the theta-gamma PAC strength of CA3-CA1 pathway in ischemia rats, which may futher improve the information transmission within the hippocampus. These results illustrated the potential electrophysiologic mechanism of VEGF on cognitive improvement.


Assuntos
Isquemia Encefálica/fisiopatologia , Região CA1 Hipocampal/metabolismo , Região CA3 Hipocampal/metabolismo , Fator A de Crescimento do Endotélio Vascular/uso terapêutico , Administração Intranasal , Animais , Isquemia Encefálica/metabolismo , Estenose das Carótidas , Doença Crônica , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/terapia , Ritmo Gama/efeitos dos fármacos , Masculino , Potenciais da Membrana/efeitos dos fármacos , Modelos Animais , Distribuição Aleatória , Ratos , Ratos Wistar , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/farmacologia , Proteínas Recombinantes/uso terapêutico , Método Simples-Cego , Ritmo Teta/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/administração & dosagem , Fator A de Crescimento do Endotélio Vascular/farmacologia , Fator A de Crescimento do Endotélio Vascular/fisiologia
11.
Cereb Cortex ; 31(4): 2058-2070, 2021 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-33283856

RESUMO

Speaking in sentences requires selection from contextually determined lexical representations. Although posterior temporal cortex (PTC) and Broca's areas play important roles in storage and selection, respectively, of lexical representations, there has been no direct evidence for physiological interactions between these areas on time scales typical of lexical selection. Using intracranial recordings of cortical population activity indexed by high-gamma power (70-150 Hz) modulations, we studied the causal dynamics of cortical language networks while epilepsy surgery patients performed a sentence completion task in which the number of potential lexical responses was systematically varied. Prior to completion of sentences with more response possibilities, Broca's area was not only more active, but also exhibited more local network interactions with and greater top-down influences on PTC, consistent with activation of, and competition between, more lexical representations. These findings provide the most direct experimental support yet for network dynamics playing a role in lexical selection among competing alternatives during speech production.


Assuntos
Área de Broca/fisiologia , Eletrocorticografia/métodos , Ritmo Gama/fisiologia , Idioma , Fala/fisiologia , Lobo Temporal/fisiologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estimulação Luminosa/métodos , Tempo de Reação/fisiologia
12.
Nature ; 590(7844): 115-121, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33299180

RESUMO

Behavioural experiences activate the FOS transcription factor in sparse populations of neurons that are critical for encoding and recalling specific events1-3. However, there is limited understanding of the mechanisms by which experience drives circuit reorganization to establish a network of Fos-activated cells. It is also not known whether FOS is required in this process beyond serving as a marker of recent neural activity and, if so, which of its many gene targets underlie circuit reorganization. Here we demonstrate that when mice engage in spatial exploration of novel environments, perisomatic inhibition of Fos-activated hippocampal CA1 pyramidal neurons by parvalbumin-expressing interneurons is enhanced, whereas perisomatic inhibition by cholecystokinin-expressing interneurons is weakened. This bidirectional modulation of inhibition is abolished when the function of the FOS transcription factor complex is disrupted. Single-cell RNA-sequencing, ribosome-associated mRNA profiling and chromatin analyses, combined with electrophysiology, reveal that FOS activates the transcription of Scg2, a gene that encodes multiple distinct neuropeptides, to coordinate these changes in inhibition. As parvalbumin- and cholecystokinin-expressing interneurons mediate distinct features of pyramidal cell activity4-6, the SCG2-dependent reorganization of inhibitory synaptic input might be predicted to affect network function in vivo. Consistent with this prediction, hippocampal gamma rhythms and pyramidal cell coupling to theta phase are significantly altered in the absence of Scg2. These findings reveal an instructive role for FOS and SCG2 in establishing a network of Fos-activated neurons via the rewiring of local inhibition to form a selectively modulated state. The opposing plasticity mechanisms acting on distinct inhibitory pathways may support the consolidation of memories over time.


Assuntos
Rede Nervosa/citologia , Rede Nervosa/fisiologia , Inibição Neural , Plasticidade Neuronal/fisiologia , Proteínas Proto-Oncogênicas c-fos/metabolismo , Animais , Região CA1 Hipocampal/metabolismo , Colecistocinina/metabolismo , Comportamento Exploratório/fisiologia , Feminino , Ritmo Gama , Interneurônios/metabolismo , Masculino , Consolidação da Memória , Camundongos , Parvalbuminas/metabolismo , Células Piramidais/metabolismo , Secretogranina II/genética , Secretogranina II/metabolismo , Navegação Espacial/fisiologia , Ritmo Teta
13.
Acta Neurochir (Wien) ; 163(5): 1299-1309, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33222010

RESUMO

BACKGROUND: Intraoperative functional mapping with direct electrical stimulation during awake surgery for patients with diffuse low-grade glioma has been used in recent years to optimize the balance between surgical resection and quality of life following surgery. Mapping of executive functions is particularly challenging because of their complex nature, with only a handful of reports published so far. Here, we propose the recording of neural activity directly from the surface of the brain using electrocorticography to map executive functions and demonstrate its feasibility and potential utility. METHODS: To track a neural signature of executive function, we recorded neural activity using electrocorticography during awake surgery from the frontal cortex of three patients judged to have an appearance of diffuse low-grade glioma. Based on existing functional magnetic resonance imaging (fMRI) evidence from healthy participants for the recruitment of areas associated with executive function with increased task demands, we employed a task difficulty manipulation in two counting tasks performed intraoperatively. Following surgery, the data were extracted and analyzed offline to identify increases in broadband high-gamma power with increased task difficulty, equivalent to fMRI findings, as a signature of activity related to executive function. RESULTS: All three patients performed the tasks well. Data were recorded from five electrode strips, resulting in data from 15 channels overall. Eleven out of the 15 channels (73.3%) showed significant increases in high-gamma power with increased task difficulty, 26.6% of the channels (4/15) showed no change in power, and none of the channels showed power decrease. High-gamma power increases with increased task difficulty were more likely in areas that are within the canonical frontoparietal network template. CONCLUSIONS: These results are the first step toward developing electrocorticography as a tool for mapping of executive function complementarily to direct electrical stimulation to guide resection. Further studies are required to establish this approach for clinical use.


Assuntos
Mapeamento Encefálico , Neoplasias Encefálicas/fisiopatologia , Neoplasias Encefálicas/cirurgia , Eletrocorticografia , Função Executiva , Glioma/fisiopatologia , Glioma/cirurgia , Cuidados Intraoperatórios , Adulto , Neoplasias Encefálicas/diagnóstico por imagem , Cognição/fisiologia , Estimulação Elétrica , Feminino , Ritmo Gama/fisiologia , Glioma/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Qualidade de Vida
14.
Clin Neurophysiol ; 131(12): 2851-2860, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33137575

RESUMO

OBJECTIVE: A novel analytic approach for task-related high-gamma modulation (HGM) in stereo-electroencephalography (SEEG) was developed and evaluated for language mapping. METHODS: SEEG signals, acquired from drug-resistant epilepsy patients during a visual naming task, were analyzed to find clusters of 50-150 Hz power modulations in time-frequency domain. Classifier models to identify electrode contacts within the reference neuroanatomy and electrical stimulation mapping (ESM) speech/language sites were developed and validated. RESULTS: In 21 patients (9 females), aged 4.8-21.2 years, SEEG HGM model predicted electrode locations within Neurosynth language parcels with high diagnostic odds ratio (DOR 10.9, p < 0.0001), high specificity (0.85), and fair sensitivity (0.66). Another SEEG HGM model classified ESM speech/language sites with significant DOR (5.0, p < 0.0001), high specificity (0.74), but insufficient sensitivity. Time to largest power change reliably localized electrodes within Neurosynth language parcels, while, time to center-of-mass power change identified ESM sites. CONCLUSIONS: SEEG HGM mapping can accurately localize neuroanatomic and ESM language sites. SIGNIFICANCE: Predictive modelling incorporating time, frequency, and magnitude of power change is a useful methodology for task-related HGM, which offers insights into discrepancies between HGM language maps and neuroanatomy or ESM.


Assuntos
Mapeamento Encefálico/normas , Epilepsia Resistente a Medicamentos/diagnóstico , Epilepsia Resistente a Medicamentos/fisiopatologia , Eletroencefalografia/normas , Idioma , Técnicas Estereotáxicas/normas , Adolescente , Mapeamento Encefálico/métodos , Criança , Pré-Escolar , Eletroencefalografia/métodos , Feminino , Ritmo Gama/fisiologia , Humanos , Masculino , Estimulação Luminosa/métodos , Estudos Prospectivos , Reprodutibilidade dos Testes , Adulto Jovem
15.
Neural Plast ; 2020: 1703969, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32774353

RESUMO

The aging process eventually cause a breakdown in critical synaptic plasticity and connectivity leading to deficits in memory function. The olfactory bulb (OB) and the hippocampus, both regions of the brain considered critical for the processing of odors and spatial memory, are commonly affected by aging. Using an aged wild-type C57B/6 mouse model, we sought to define the effects of aging on hippocampal plasticity and the integrity of cortical circuits. Specifically, we measured the long-term potentiation of high-frequency stimulation (HFS-LTP) at the Shaffer-Collateral CA1 pyramidal synapses. Next, local field potential (LFP) spectra, phase-amplitude theta-gamma coupling (PAC), and connectivity through coherence were assessed in the olfactory bulb, frontal and entorhinal cortices, CA1, and amygdala circuits. The OB of aged mice showed a significant increase in the number of histone H2AX-positive neurons, a marker of DNA damage. While the input-output relationship measure of basal synaptic activity was found not to differ between young and aged mice, a pronounced decline in the slope of field excitatory postsynaptic potential (fEPSP) and the population spike amplitude (PSA) were found in aged mice. Furthermore, aging was accompanied by deficits in gamma network oscillations, a shift to slow oscillations, reduced coherence and theta-gamma PAC in the OB circuit. Thus, while the basal synaptic activity was unaltered in older mice, impairment in hippocampal synaptic transmission was observed only in response to HFS. However, age-dependent alterations in neural network appeared spontaneously in the OB circuit, suggesting the neurophysiological basis of synaptic deficits underlying olfactory processing. Taken together, the results highlight the sensitivity and therefore potential use of LFP quantitative network oscillations and connectivity at the OB level as objective electrophysiological markers that will help reveal specific dysfunctional circuits in aging-related neurodegeneration studies.


Assuntos
Envelhecimento/fisiologia , Região CA1 Hipocampal/fisiologia , Bulbo Olfatório/fisiologia , Células Piramidais/fisiologia , Animais , Dano ao DNA , Ritmo Gama , Potenciação de Longa Duração , Masculino , Camundongos Endogâmicos C57BL , Vias Neurais , Ritmo Teta
16.
Epilepsy Res ; 166: 106375, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32745888

RESUMO

Chronic intermittent hypoxia (CIH) is the most distinct feature of obstructive sleep apnea (OSA), a common breathing and sleep disorder that leads to several neuropathological consequences, including alterations in the hippocampal network and in seizure susceptibility. However, it is currently unknown whether these alterations are permanent or remit upon normal oxygenation. Here, we investigated the effects of CIH on hippocampal spontaneous network activity and hyperexcitability in vitro and explored whether these alterations endure or fade after normal oxygenation. Results showed that applying CIH for 21 days to adult rats increases gamma-band hippocampal network activity and aggravates 4-Aminopyridine-induced epileptiform activity in vitro. Interestingly, these CIH-induced alterations remit after 30 days of normal oxygenation. Our findings indicate that hippocampal network alterations and increased seizure susceptibility induced by CIH are not permanent and can be spontaneously reverted, suggesting that therapeutic interventions against OSA in patients with epilepsy, such as surgery or continuous positive airway pressure (CPAP), could be favorable for seizure control.


Assuntos
4-Aminopiridina/toxicidade , Ritmo Gama/fisiologia , Hipocampo/fisiopatologia , Hipóxia Encefálica/fisiopatologia , Rede Nervosa/fisiopatologia , Animais , Doença Crônica , Ritmo Gama/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Hipóxia Encefálica/complicações , Masculino , Rede Nervosa/efeitos dos fármacos , Técnicas de Cultura de Órgãos , Bloqueadores dos Canais de Potássio/toxicidade , Ratos , Ratos Wistar , Convulsões/induzido quimicamente , Convulsões/etiologia , Convulsões/fisiopatologia
17.
Genes Brain Behav ; 19(6): e12678, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32468668

RESUMO

The activated mammalian Ste20-like serine/threonine kinases 1 (MST1) was found in the central nervous system diseases, such as cerebral ischemia, stroke and ALS, which were related with cognitions. The aim of this study was to examine the effect of elevated MST1 on memory functions in C57BL/6J mice. We also explored the underlying mechanism about the pattern alteration of neural oscillations, closely associated with cognitive dysfunctions, at different physiological rhythms, which were related to a wide range of basic and higher-level cognitive activities. A mouse model of the adeno-associated virus (AAV)-mediated overexpression of MST1 was established. The behavioral experiments showed that spatial memory was significantly damaged in MST1 mice. The distribution of either theta or gamma power was clearly disturbed in MST1 animals. Moreover, the synchronization in both theta and gamma rhythms, and theta-gamma cross-frequency coupling were significantly weakened in MST1 mice. In addition, the expressions of GABAA receptor, GAD67 and parvalbumin (PV) were obviously increased in MST1 mice. Meanwhile, blocking MST1 activity could inhibit the activation of FOXO3a and YAP. The above data suggest that MST1-overexpression may induce memory impairments via disturbing the patterns of neural activities, which is possibly associated with the abnormal GABAergic expression level.


Assuntos
Ritmo Gama , Proteínas Serina-Treonina Quinases/genética , Memória Espacial , Ritmo Teta , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Encéfalo/metabolismo , Encéfalo/fisiologia , Cognição , Proteína Forkhead Box O3/metabolismo , Glutamato Descarboxilase/genética , Glutamato Descarboxilase/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Parvalbuminas/genética , Parvalbuminas/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Receptores de GABA-A/genética , Receptores de GABA-A/metabolismo , Regulação para Cima , Proteínas de Sinalização YAP
18.
Neuroimage ; 210: 116548, 2020 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-31958582

RESUMO

Lower- and higher-order visual cortices in the posterior brain, ranging from the medial- and lateral-occipital to fusiform regions, are suggested to support visual object recognition, whereas the frontal eye field (FEF) plays a role in saccadic eye movements which optimize visual processing. Previous studies using electrophysiology and functional MRI techniques have reported that tasks requiring visual object recognition elicited cortical activation sequentially in the aforementioned posterior visual regions and FEFs. The present study aims to provide unique evidence of direct effective connectivity outgoing from the posterior visual regions by measuring the early component (10-50 â€‹ms) of cortico-cortical spectral responses (CCSRs) elicited by weak single-pulse direct cortical electrical stimulation. We studied 22 patients who underwent extraoperative intracranial EEG recording for clinical localization of seizure foci and functionally-important brain regions. We used animations to visualize the spatiotemporal dynamics of gamma band CCSRs elicited by stimulation of three different posterior visual regions. We quantified the strength of CCSR-defined effective connectivity between the lower- and higher-order posterior visual regions as well as from the posterior visual regions to the FEFs. We found that effective connectivity within the posterior visual regions was larger in the feedforward (i.e., lower-to higher-order) direction compared to the opposite direction. Specifically, connectivity from the medial-occipital region was largest to the lateral-occipital region, whereas that from the lateral-occipital region was largest to the fusiform region. Among the posterior visual regions, connectivity to the FEF was largest from the lateral-occipital region and the mean peak latency of CCSR propagation from the lateral-occipital region to FEF was 26 â€‹ms. Our invasive study of the human brain using a stimulation-based intervention supports the model that the posterior visual regions have direct cortico-cortical connectivity pathways in which neural activity is transferred preferentially from the lower-to higher-order areas. The human brain has direct cortico-cortical connectivity allowing a rapid transfer of neural activity from the lateral-occipital region to the FEF.


Assuntos
Conectoma , Eletrocorticografia , Potenciais Evocados/fisiologia , Córtex Pré-Frontal/fisiologia , Percepção Visual/fisiologia , Adolescente , Adulto , Criança , Estimulação Elétrica , Epilepsia/fisiopatologia , Epilepsia/cirurgia , Feminino , Ritmo Gama/fisiologia , Humanos , Masculino , Vias Neurais/diagnóstico por imagem , Vias Neurais/fisiologia , Córtex Pré-Frontal/diagnóstico por imagem , Fatores de Tempo , Adulto Jovem
19.
Clin Neurophysiol ; 131(1): 330-342, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31506235

RESUMO

OBJECTIVE: Altered brain functional connectivity has been shown in youth with attention-deficit/hyperactivity disorder (ADHD). However, relatively little is known about functional connectivity in adult ADHD, and how it is linked with the heritability of ADHD. METHODS: We measured eyes-open and eyes-closed resting electroencephalography (EEG) from 38 adults with ADHD, 45 1st degree relatives of people with ADHD and 51 healthy controls. Functional connectivity among all scalp channels was calculated using a weighted phase lag index for delta, theta, alpha, beta and gamma frequency bands. A machine learning analysis using penalized linear regression was used to identify if connectivity features (10,080 connectivity pairs) could predict ADHD symptoms. Furthermore, we examined if EEG connectivity could accurately classify participants into ADHD, 1st degree relatives and/or control groups. RESULTS: Hyperactive symptoms were best predicted by eyes-open EEG connectivity in delta, beta and gamma bands. Inattentive symptoms were predicted by eyes-open EEG connectivity in delta, alpha and gamma bands, and eyes-closed EEG connectivity in delta and gamma bands. EEG connectivity features did not reliably classify participants into groups. CONCLUSIONS: EEG connectivity may represent a neuromarker for ADHD symptoms. SIGNIFICANCE: EEG connectivity may help elucidate the neural basis of adult ADHD symptoms.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Conectoma , Eletroencefalografia/métodos , Adulto , Ritmo alfa/fisiologia , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Ritmo beta/fisiologia , Estudos de Casos e Controles , Ritmo Delta/fisiologia , Feminino , Ritmo Gama/fisiologia , Humanos , Modelos Lineares , Aprendizado de Máquina , Masculino , Pais , Transtornos da Percepção/fisiopatologia , Agitação Psicomotora/fisiopatologia , Irmãos , Avaliação de Sintomas , Ritmo Teta/fisiologia
20.
Einstein (Säo Paulo) ; 18: eAO5442, 2020. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1133738

RESUMO

ABSTRACT Objective: To verify if, by three distinct quantifiers, the measured electroencephalographic signal at rest is different from the signal measured during a word reading situation, especially considering the faster rhythms, gamma and high-gamma, as it occurs in clinical rhythms (delta to beta). Methods: A total of 96 electroencephalographic signals measured from neurologically healthy volunteers were evaluated at two moments: resting and word reading. Each signal segment was measured by three quantifiers that separately assess normalized power, percent power, and right and left hemisphere coherence. The Mann-Whitney test was used to compare the results of the quantifiers in each brain range. Results: The gamma and high-gamma rhythms presented a more distinct behavior when comparing the analyzed moments (resting and reading) than the clinical rhythms. Conclusion: This finding contributes to the scarce literature on faster rhythms, which can contain information that is normally disregarded in neurological clinical practice.


RESUMO Objetivo: Verificar se, por meio de três quantificadores distintos, o sinal eletroencefalográfico medido em repouso é diferente do sinal medido durante o processo de leitura, especialmente considerando os ritmos rápidos, gama e supergama, assim como ocorre nos ritmos clínicos delta a beta. Métodos: Foram avaliados 96 sinais eletroencefalográficos medidos em voluntários neurologicamente saudáveis, em dois momentos: repouso e leitura de palavras. Cada trecho do sinal foi mensurado por três quantificadores que medem, de maneira isolada, a potência normalizada e a potência percentual, bem como a coerência entre os hemisférios direito e esquerdo. O teste estatístico de Mann-Whitney foi usado para comparar os resultados dos quantificadores em cada faixa cerebral. Resultados: Os ritmos gama e supergama apresentaram comportamento mais distinto entre os momentos analisados (repouso e leitura) que os ritmos clinicamente analisados. Conclusão: Esse achado contribui com a escassa literatura segundo a qual os ritmos rápidos podem conter informações que normalmente são descartadas na neurologia clínica.


Assuntos
Leitura , Encéfalo/diagnóstico por imagem , Eletroencefalografia/métodos , Ritmo Gama , Ritmo beta , Ritmo Delta
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